Evaluation of mono and combined nitrofurantoin therapy for toxoplasmosis in vivo using murine model

Toxoplasmosis is a frequent disease with an estimated prevalence of more than one billion human cases worldwide and over one million new infections each year. It is classified as a neglected tropical disease by the CDC since 2019. The disease may pass unnoticed in healthy individuals but could be fatal in the immunocompromised. Moreover, no effective treatment is available against the chronic form of the disease. Available anti-Toxoplasma drugs are associated with many side effects. Therefore, search for new more reliable, more efficient, and less toxic therapeutic agents is a continuous endeavor. This study assesses the potential use of nitrofurantoin, a compound with well-established antimicrobial properties, as a potential anti-Toxoplasma drug in vivo. It compares its efficacy to the commonly used anti-Toxoplasma agent spiramycin by molecular and histopathological methods in acute and chronic infection. The results demonstrate a significant ability to eliminate the parasite (P < 0.001) whether used as mono- or combined therapy with spiramycin in the acute and chronic stages. When compared to the anti-Toxoplasma drug spiramycin, nitrofurantoin achieved similar efficacy in the acute and chronic infection (P = 0.65 and P = 0.096, respectively). However, better results were obtained when using a combination of both drugs (P < 0.001). Additionally, nitrofurantoin showed good inhibitory effects on the inflammatory process in the liver, kidney, and uterus of the experimentally infected animals. In conclusion, nitrofurantoin can be considered as a potential anti-Toxoplasma agent. Nevertheless, further studies are recommended before consideration for clinical trials.